In 1974, du Cann played a part in the events surrounding the elevation of Margaret Thatcher to the leadership of the Conservative Party. Following two narrow defeats for the Conservatives at the polls, in February and October 1974, significant disquiet in the party had developed over the leadership of Edward Heath, who had lost three elections as leader. On 14 October 1974, the executive of the 1922 Committee met at du Cann's home, amidst a good deal of press attention.

That was soon followed by a more public meeting of the executive at du Cann's offices at Keyser Ullman, on Milk Street, where it was decided that the Committee would press Heath to hold a leadership election. The location of this meeting led to Fleet Street nicknaming the attendees the "Milk Street Mafia". As Alec Douglas-Home, at Heath's request, considered the procedures for a leadership election, there was some speculation that du Cann would himself stand as a representative of the party's right-wing against Heath.[citation needed]

By the time Douglas-Home reported in December 1974, however, events had intervened. The devastating collapse of the banking boom had swept up du Cann's firm, Keyser Ullman, in its path.[citation needed] He was criticized as "incompetent" by a 1974 Department of Trade and Industry report regarding the bankrupt Keyser Ullman bank, of which he was a director.[4] Du Cann did not put himself forward as a candidate in the leadership contest. This released key support for Margaret Thatcher, especially as another potential right-wing candidate, Keith Joseph, withdrew from any leadership attempt following a series of controversial speeches on social policy. Consequently, after defeating Heath in the first round, Thatcher emerged triumphant in the second round in early 1975, defeating a number of other candidates who would play significant roles in her subsequent premiership.[5]

Du Cann succeeded Duncan Sandys as chairman of Lonrho, a position from which he was forced to resign due to his role as deputy chairman of Homes Assured, a finance company which crashed.[4] His resignation came two days before the company collapsed, owing £10 million to creditors.[8] Du Cann was involved in several legal disputes over debts; his Somerset estate was repossessed in 1992 and his London flat was repossessed in 1993. He later had a bankruptcy order served against him.[9]

He was a board member of E-Clear, a British payment processing company, which went into administration in January 2010.[10] He married three times; first, in 1962, to Sally (a cousin), whom he divorced in 1987, then to Jennifer (the widow of Robert Cooke, former MP for Bristol West), whom he married in 1990 and was with until her death in 1995.[11] He was declared bankrupt in 1993 and lived for several years in Alderney. As of 2013 he was a resident of Lemona in Cyprus.[12] He is survived by his third wife, Maureen Hope-Wynne.